Effect of nifedipine on endothelin induced contractions of skeletal muscle arterioles of spontaneously hypertensive rats.
Endothelin is a potent vasoactive polypeptide isolated from cultured endothelial cells. However, there are relatively few studies of the action of endothelin on microvessels in vivo. To determine the effects of this compound on arterioles of normotensive and hypertensive rats, endothelin (1 x 10(-12) M to 1 x 10(-8) M) was dissolved in physiological salt solution and superfused over the cremaster muscle of 12-15 week old spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. Endothelin caused about a 55% constriction of second order arterioles and complete closure of most third order arterioles and all fourth order arterioles studied. SHR arterioles tended to be more sensitive to endothelin than those of WKY, although this difference was significant for only the third order arterioles. Endothelin induced contractions were significantly inhibited by 10(-6) M nifedipine in both WKY and SHR. These studies demonstrate that endothelin is a potent constrictor of skeletal muscle arterioles, and suggest that activator Ca2+ for endothelin induced contractions of these vessels enters the vascular smooth muscle cells through dihydropyridine sensitive calcium channels.
Lougee
L
L
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Hinojosa-Laborde
C
C
Harder
D R
DR
Lombard
J H
JH
D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009132:Muscles / Q000098:blood supply*; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D009543:Nifedipine; D002118:Calcium